γδ T Cell-Deficient Mice Have a Down-Regulated CD8+ T Cell Immune Response Against Encephalitozoon cuniculi Infection

Abstract

γδ T cells have been reported to play an essential effector role during the early immune response against a wide variety of infectious agents. Recent studies have suggested that the γδ T cell subtype may also be important for the induction of adaptive immune response against certain microbial pathogens. In the present study, an early increase of γδ T cells during murine infection with Encephalitozoon cuniculi, an intracellular parasite, was observed. The role of γδ T cells against E. cuniculi infection was further evaluated by using gene-knockout mice. Mice lacking γδ T cells were susceptible to E. cuniculi infection at high challenge doses. The reduced resistance of δ−/− mice was attributed to a down-regulated CD8+ immune response. Compared with parental wild-type animals, suboptimal Ag-specific CD8+ T cell immunity against E. cuniculi infection was noted in δ−/− mice. The splenocytes from infected knockout mice exhibited a lower frequency of Ag-specific CD8+ T cells. Moreover, adoptive transfer of immune TCRαβ+ CD8+ T cells from the δ−/− mice failed to protect naive CD8−/− mice against a lethal E. cuniculi challenge. Our studies suggest that γδ T cells, due to their ability to produce cytokines, are important for the optimal priming of CD8+ T cell immunity against E. cuniculi infection. This is the first evidence of a parasitic infection in which down-regulation of CD8+ T cell immune response in the absence of γδ T cells has been demonstrated.